Miller K, Abeles G, Oratz R, Zeleniuch-Jacquotte A, Cui J, Roses D F, Harris M N, Bystryn J C
New York University School of Medicine, Ronald O. Perelman Department of Dermatology, NY 10016.
Cancer. 1995 Jan 15;75(2):495-502. doi: 10.1002/1097-0142(19950115)75:2<495::aid-cncr2820750212>3.0.co;2-s.
Melanoma vaccine treatment appears to slow the progression of melanoma in some patients, particularly in patients in whom it stimulates cellular antimelanoma immune responses. The relationship of vaccine-induced antibody responses to clinical outcome is less clear. The purpose of this study was to investigate the clinical relevance of antibody responses to melanoma vaccine immunization.
Eighty-two evaluable patients with surgically resected American Joint Committee on Cancer Stage III malignant melanoma were immunized to a partially purified, polyvalent, melanoma antigen vaccine. Antimelanoma antibodies were measured by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis before vaccine treatment and 1 week after the fourth immunization.
Vaccine treatment induced or augmented antibody responses to melanoma in 32 (39%) of the patients. The antibodies were directed to one or more antigens of 38-43, 75, 110, 150 and/or 210 kDs, which previously have been shown to be expressed preferentially in cultured human melanoma cells. The median disease free survival of patients with a vaccine-induced antibody response to one or more of these antigens was 5.4 years compared with 1.4 years for nonresponders (P = 0.06), and 5-year overall survival was 71% compared with 44%, respectively (P = < 0.01). As determined by Cox multivariate analysis, the difference in overall survival was independent of disease severity or of immunologic competence as evaluated by ability to be sensitized to dinitrochlorobenzene. The difference in survival between antibody responders and nonresponders improved with time.
The antibody response to vaccine treatment is an immune marker of vaccine activity that appears to be predictive of a later reduction in the recurrence of melanoma and is unrelated to the vaccine's ability to induce cellular immune responses. This finding suggests that vaccine treatment may be effective in slowing the progression of melanoma in some patients and that the protective effect is mediated partly by vaccine-induced antimelanoma antibodies.
黑色素瘤疫苗治疗似乎能减缓部分患者黑色素瘤的进展，尤其是那些能刺激细胞抗黑色素瘤免疫反应的患者。疫苗诱导的抗体反应与临床结局之间的关系尚不清楚。本研究旨在探讨抗体反应对黑色素瘤疫苗免疫的临床相关性。
82例可评估的接受手术切除的美国癌症联合委员会III期恶性黑色素瘤患者接种了部分纯化的多价黑色素瘤抗原疫苗。在疫苗治疗前和第四次免疫后1周，通过免疫沉淀和十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分析测定抗黑色素瘤抗体。
疫苗治疗在32例（39%）患者中诱导或增强了对黑色素瘤的抗体反应。这些抗体针对38 - 43、75、110、150和/或210 kD的一种或多种抗原，这些抗原先前已被证明在培养的人黑色素瘤细胞中优先表达。对这些抗原中的一种或多种有疫苗诱导抗体反应的患者的无病生存期中位数为5.4年，而无反应者为1.4年（P = 0.06），5年总生存率分别为71%和44%（P = < 0.01）。通过Cox多变量分析确定，总生存率的差异与疾病严重程度或通过对二硝基氯苯致敏能力评估的免疫能力无关。抗体反应者和无反应者之间的生存差异随时间推移而改善。
对疫苗治疗的抗体反应是疫苗活性的免疫标志物，似乎可预测黑色素瘤复发率的后期降低，且与疫苗诱导细胞免疫反应的能力无关。这一发现表明，疫苗治疗可能对减缓部分患者黑色素瘤的进展有效，且保护作用部分由疫苗诱导的抗黑色素瘤抗体介导。
